William Bastian, M.D. will be trained in fundamental aspects of Biochemistry, Molecular Biology and Cell Biology. Included is intensive training in basic research on the signaling activity of the insulin receptor. The overall goal is to provide Dr. Bastian with the background necessary for him to establish a productive, independent research program that examines growth factor receptors. This program emphasizes mastery of fundamentals that underlie techniques in biochemistry, molecular biology and cell biology and theoretical considerations regarding the actions of insulin and growth factors. His training will be divided into two phases: Phase I that lasts two years and Phase II that requires three years. During Phase I, Dr. Bastian will take for credit the courses given to graduate students in biochemistry and will attend seminars, a journal club and appropriate clinical conferences. He will begin the research outlined below, which will continue throughout the five year period. During Phase II, he will concentrate on research and will attend Pediatric Endocrinology clinics (20% effort only) as well as participate in seminars, journal club and clinical conferences. The specific aims of the research that he will conduct are to: 1. Evaluate the involvement of insulin-induced autophosphorylation of Tyr 1316 and 1322 (autophosphorylation "B" domain) on acute and chronic actions of insulin by generating site-directed mutations in the insulin receptor. 2.Determine whether the receptor mutations in the "B" domain alters cycling of the insulin receptor and receptor-mediated degradation of insulin. These studies will investigate an important aspect of insulin receptor signaling activity and provide extensive research training in a large variety of basic techniques.